There is increasing evidence that the central nervous system (CNS) can influence the immune response, the body's defense against infectious and malignant disease. Data from our laboratory and others have demonstrated that an increase in psychological distress can lead to adverse immunological changes. These distress-related immunological changes provide one physiological pathway through which major and minor life changes might result in an increased incidence of infectious disease. However, most individuals undergoing even major life changes do not become ill, or they only experience short illness episodes. Actual organically-based illness episodes are a function of differential exposure to pathogens and/or carcinogens, as well as the prior health of the individual, particularly in regard to immune system function. In this Program Project Grant we have six projects, three involving human subjects, and three involving animal models, to study CNS- endocrine-immune interaction and the impact of different stressors on this interaction. Project 1 employs a medical student academic stress model that investigates different aspects of the cellular immune response, focusing on T-lymphocyte and macrophage function while simultaneously measuring certain selected hormones associated with psychological stress, in conjunction with Project 3. Project 2 addresses the endocrinological and immunological correlates of marital quality in a prospective design, in collaboration with Project 3 as well. Project 3 is an endocrine study that interacts with both Projects 1 and 2, allowing detailed studies of the CNS- endocrine-immune axis to be performed. Project 4, the first of the animal studies, addresses the effect of acute stress (cold-water swimming) on the immune response, and the impact on morbidity and mortality of mice inoculated with influenza virus. Project 5 is concerned with health-related changes associated with a microbial infection in which the immune response, specifically macrophages, play an important role. Project 6 is a study of T-lymphocyte- mediated autoimmune disease in rats that can be experimentally induced. The effect of acute stress on T-cell immunity and health outcomes of this autoimmune disease will be measured clinically and immunologically. There are also two core sections: Core A is the administrative core, and Core B is the statistical analysis and data management core. Research on the relationships between the CNS, immune system and the endocrine system will provide evidence of physiological pathways through which various kinds of stressors may modulate immune function and health.